Acetylenic amines



United States Patent f 3,156,726 ACETYLENIC AMINES Kent C. Brannoclr andRobert D. Burpitt, both of Kingsport, Tenn, assigncrs to Eastman KodakCompany, Rochester, N.Y., a corporation of New Jersey No Drawing. FiledSept. 19, 1961, Ser. No. 139,050 2 Claims. (Cl. 260-5703) This inventionrelates to organic compounds and more particularly to novel acetylenicamines.

The compounds of the invention are of the general structure wherein R isa phenyl or substituted phenyl radical, R and R are hydrogen, monovalenthydrocarbon radicals, or divalent hydrocarbon radicals which, with thecarbon atom to which they are attached, form a or 6-membered, saturatedcarbocyclic ring, and R and R are monovalent hydrocarbon radicals ordivalent organic radicals which, with the nitrogen atom to which theyare attached, form a 5- or 6-membered, saturated heterocyclic ring.

In the above formula R is preferably a phenyl radical but can also be asubstituted phenyl radical having one or more substituents such as loweralkyl radicals.

R R R and R are typically the same or different monovalent radicals suchas hydrogen or alkyl, cycloalkyl, or aryl radicals having from about 1to 8 carbon atoms. In addition, R and R can be alkylene radicals which,with the carbon atom to which they are attached, form a cyclopentyl orcyclohexyl radical. R and R can also be divalent radicals which, withthe nitrogen atom to which they are attached, form a heterocyclicradical such as morpholino, pyrrolidinyl or piperidino.

The compounds of the invention can be prepared by the reaction of anacetylenic compound with an enamine. The reaction can be represented bythe following equation:

wherein R, R R R and R are radicals of the types stated above. Thereaction can be carried out by heating approximately equimolar amountsof the reactants at reflux temperature, preferably in the presence'of acatalyst such as cuprous chloride. The reaction can also be carried outin the absence of a catalyst by heating the reactants at refluxtemperature for several hours, but the use of a catalyst is preferred toincrease the reaction rate.

Acetylenic compounds suitable for the above reaction includephenylacetylene and closely related ring-substituted phenylacetylenes,such as those having one or more lower alkyl substituents on the phenylgroup. The enamine reactant can be selected from a broad class ofenamines of the type .lCC

One type of suitable enamine is the type having no 8- hydrogen atoms,which can be prepared by reacting an aldehyde having one a-hydrogen atomwith a secondary amine. Typical enamines of this type include:N,N-dimethylisobutenylamine, N,N-diethylisobutenylamine, N,N-dibutylisobutenylamine, N-isobutenylpiperidine,N-isobutenylpyrrolidine, N,N-dimethyl-Z-methylbutenylamine, N (2methylbutenyl)piperidine, N,N dimethyl 2- ethylbutenylamine, N (2ethylbutenyhpiperidine, N- (methylenecyclohexyl)dimethylamine, N(methylenecyclohexyl)piperidine, N isobutenylmorpholine, N (2-ethylhexenyl)morpholine, N (2 ethylhexenyl)piperidine,N,N-dimethyl-2-ethylhexenylamine, and the like,

Another suitable type of enamine is the type having at least onehydrogen atom and on the B-carbon atom, which can be prepared byreacting a secondary amine with an' aldehyde having at leasttwotat-hydrogen atoms. Examples of such enamines include: N-(1-butenyl)-piperidine, N,N-dimethylvinylamine, N,N-dimethylpropenylamine,N-(l-butenyl)pyrrolidine, N,N-dimethyl-lbutenylamine, N,N dibutyl 1butenylamine, N (1- heptenyl)morpholine, and the like.

Our invention is illustrated by the following examples:

Example 1 Example 2 N,N-dimethylisobutenylamine (25 g.), cuprouschloride (1 g.) and phenyl acetylene (25 g.) were combined. There was amild evolution of heat, and the temperature rose to 46 over a /2-hourperiod. The flask was then warmed gently on the steam bath and anexothermic reaction took place with the temperature rising to in about 5minutes. The mixture was cooled, filtered and distilled to give 34 g.(68%) of 3-dimethylamino-4- methyl-l-phenyl-l-pentyne.

The novel compounds of our invention are useful as pharmaceuticals andas pharmaceutical intermediates. For example,3-dimethylamino-4-methyl-l-phenyl-l-pentyne is useful as an analgesic.It can also be converted to its non-toxic acid salts such as thehydrochloride salt, the phosphate or the citrate for pharmaceutical use,particularly as an analgesic.

The invention has been described in detail with particular reference topreferred embodiments thereof, but it will be understood that variationsand modifications can be eifected within the spirit and scope of theinvention as described hereinabove and as defined in the appendedclaims.

We claim:

1. Compounds of the formula t t RCECCI3(IL-R2 N R3 R4 R wherein R isselected from the group consisting of phenyl and lower alkyl-substitutedphenyl radicals; R and R Patented Nov. 10, 1954 3 4 are selected fromthe group consisting of hydrogen, saturated heterocyclic ring from thegroup consisting alkyl radicals of one to eight carbon atoms, andalkylene of morpholino, pyrrolidinyl and piperidino. radicals which,with the carbon atom to which they are 2.3-dimethylamino-4-methyl-1-phenyl-l-pentyne. attached, form a 5- too-membered saturated carbocyclic ring; and R and R are selected from thegroup consist- 5 References Cited in the file of this patent ing ofalkyl radicals of one to eight carbon atoms and UNITED STATES PATENTSdivalent organic radicals which, with the nitrogen atom to which theyare attached, form a 5- tO 6-membered, 3007933 Hennion 1961

1. COMPOUNDS OF THE FORMULA